What question did this study set out to answer?

To verify the cortical damage induced by recent small subcortical infarcts and its clinical associations.

March 23, 2026Open Access

Remote cortical degeneration related to structural connectivity following recent small subcortical infarcts

Key Points

To verify the cortical damage induced by recent small subcortical infarcts and its clinical associations.
Included RSSI patients with longitudinal MRI.
Assessed cortical degeneration using linear mixed-effects models.
Employed PCA to extract features of cortical alterations.
Analyzed associations with neuroimaging markers and clinical outcomes.
RSSI induces progressive cortical thinning and volume loss in connected regions.
PCA identified atrophy linked to white matter integrity and track/cap signs.
Faster cortical degeneration correlates with higher Hamilton Anxiety Rating Scale scores.

Abstract

• RSSI causes remote cortical atrophy via structural connectivity. • White matter integrity predicts cortical atrophy rate. • Atrophy in lesion-connected cortex relates to HAMA worsening. • Subject-specific dMRI and normative connectomes yield similar findings. Secondary cortical degeneration caused by the remote effects of subcortical infarcts has been implicated in long-term outcomes after acute ischemic stroke. However, this process remains insufficiently studied in recent small subcortical infarcts (RSSI). We aimed to verify RSSI-induced cortical damage, determine whether it can be captured by neuroimaging markers, and explore its association with clinical outcomes. RSSI patients with longitudinal Magnetic Resonance Imaging (MRI) were included. Cortical degeneration was assessed using linear mixed-effects models, incorporating a direct approach based on individual diffusion weighted imaging and an indirect approach using the normative connectome from the Human Connectome Project (HCP). Principal component analysis (PCA) was employed to extract features of cortical alterations. The resulting component scores were used in general linear models to assess associations with neuroimaging markers and clinical outcomes. A total of 76 RSSI patients were analyzed. RSSI was found to induce progressive cortical thinning and volume loss in structurally connected regions. PCA identified a component reflecting parenchymal atrophy associated with diffusion-based markers of white matter integrity, as well as the presence of track/cap signs. Moreover, faster cortical degeneration in lesion-connected regions was significantly associated with a greater increase in Hamilton Anxiety Rating Scale (HAMA) scores (β = -2.38, 95% CI = -4.30 – −0.47, p = 0.017). RSSI induces secondary cortical damage through structurally connected fiber tracts, which is detectable by neuroimaging markers of white matter integrity. These regional cortical alterations may be relevant to post-stroke outcomes and require validation in larger longitudinal studies.

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